Effects of ethanol on liver microtubules and Golgi apparatus. Possible role in altered hepatic secretion of plasma proteins

Abstract

A combined morphometric and biochemical approach was used to study the effects of alcohol on hepatic microtubules. Feeding of ethanol-containing diets to rats decreased the amount of polymerized tubulin and the number of visible microtubules, and it also produced morphologic alterations of this organelle. These microtubular alterations were reproduced in isolated hepatocytes after incubation with ethanol. Pyrazole, an inhibitor of alcohol dehydrogenase, prevented these effects. Two oxidation products of ethanol, acetaldehyde and acetate, in concentrations likely to occur "in vivo" also reproduced the effects of ethanol on microtubules. The alterations of microtubules, induced by either ethanol or its metabolites, were associated with significant increases in the volume and surface densities of the Golgi complex. Moreover, both the microtubular and the Golgi alterations were prevented by inhibiting the oxidation of ethanol with pyrazole, an inhibitor of alcohol dehydrogenase. These findings indicate that ethanol oxidation alters liver microtubules; as a likely result, delayed secretion of export proteins ensues with early retention in the Golgi vesicles. After chronic alcohol feeding, there was also a significant increase in the volume of the cytoplasm, which could reflect retention of soluble proteins and water.